Project Summary: Nontuberculous Mycobacteria (NTM) infection in cystic fibrosis (CF) is common, particularly Mycobacterium avium complex (MAC) and M. abscessus complex and appears to be increasing in prevalence. New approaches are needed as current drug regimens involve prolonged administration of drugs with significant toxicity and rates of treatment failure are high. Despite prolonged courses of multidrug therapy, effective cure for MAC lung disease is just under 60% in subjects without immune suppression or CF. In regard to M. abscessus complex, treatment response has been variable. M. abscessus ssp. massiliense demonstrated a better treatment response with more sustained negative cultures compared to M. abscessus ssp. abscessus (88 vs 25%) in non-CF disease. Thus, novel treatments are needed to improve clinical outcomes. While still controversial, recent evidence supporting patient to patient spread of M. abscessus complex in CF centers raises the urgency of development of better treatments in CF. We propose to exploit the iron vulnerability of both MAC and M. abscessus complex by using the metal gallium as a Trojan horse to disrupt iron metabolism. Gallium has a nearly identical ionic radius as Fe, and some bacterial uptake systems are unable to distinguish gallium from iron. Gallium disrupts iron-dependent processes because Ga3+ cannot be reduced in physiological conditions, and iron's biological functions involves redox cycling. Thus, gallium incorporation into iron-containing proteins disrupts their functioning. Previous work by our group and others found that gallium compounds had antibacterial activity against a number of human pathogens including Pseudomonas aeruginosa, Fransella tulerensis, Acinetobacter baumanai, Klebsiella pneumoniae, and other important pathogens including MAC and M. abscessus complex. Our prior trials (phase 1b and 2b) in CF patients infected with P. aeruginosa demonstrated that a single course of IV gallium was safe and showed evidence of efficacy. Here we propose a phase 1b open label phase 1b bridging study to assess the safety and pharmacokinetics of two sequential 5-day infusions of gallium nitrate in adults with CF who are infected with either MAC and M. abscessus complex at a dose of 200 mg/m2/day. We will also assess for preliminary microbiologic effect using the study population and a contemporary control population enrolled in a parent observational PREDICT trial (PRospective Evaluation of NTM Disease In CysTic Fibrosis; NCT02073409), a 10 center observational study of NTM in CF funded by the US CF Foundation.